Allo Beta Cell transplantation: specific features, unanswered questions, and immunological challenge

Type 1 diabetes (T1D) presents a persistent medical challenge, demanding innovative strategies for sustained glycemic control and enhanced patient well-being. Beta cells are specialized cells in the pancreas that produce insulin, a hormone that regulates blood sugar levels. When beta cells are damaged or destroyed, insulin production decreases, which leads to T1D. Allo Beta Cell Transplantation has emerged as a promising therapeutic avenue, with the goal of reinstating glucose regulation and insulin production in T1D patients. However, the path to success in this approach is fraught with complex immunological hurdles that demand rigorous exploration and resolution for enduring therapeutic efficacy. This exploration focuses on the distinct immunological characteristics inherent to Allo Beta Cell Transplantation. An understanding of these unique challenges is pivotal for the development of effective therapeutic interventions. The critical role of glucose regulation and insulin in immune activation is emphasized, with an emphasis on the intricate interplay between beta cells and immune cells. The transplantation site, particularly the liver, is examined in depth, highlighting its relevance in the context of complex immunological issues. Scrutiny extends to recipient and donor matching, including the utilization of multiple islet donors, while also considering the potential risk of autoimmune recurrence. Moreover, unanswered questions and persistent gaps in knowledge within the field are identified. These include the absence of robust evidence supporting immunosuppression treatments, the need for reliable methods to assess rejection and treatment protocols, the lack of validated biomarkers for monitoring beta cell loss, and the imperative need for improved beta cell imaging techniques. In addition, attention is drawn to emerging directions and transformative strategies in the field. This encompasses alternative immunosuppressive regimens and calcineurin-free immunoprotocols, as well as a reevaluation of induction therapy and recipient preconditioning methods. Innovative approaches targeting autoimmune recurrence, such as CAR Tregs and TCR Tregs, are explored, along with the potential of stem stealth cells, tissue engineering, and encapsulation to overcome the risk of graft rejection. In summary, this review provides a comprehensive overview of the inherent immunological obstacles associated with Allo Beta Cell Transplantation. It offers valuable insights into emerging strategies and directions that hold great promise for advancing the field and ultimately improving outcomes for individuals living with diabetes

Renal toxicity and osteonecrosis of the jaw in cancer patients treated with bisphosphonates: a long-term retrospective analysis.

BACKGROUND: Bisphosphonates (BPs) are the mainstay of bone-directed therapy for bone metastases from multiple myelomas and a wide range of solid tumours, but some patients experience renal toxicity or osteonecrosis of the jaw (ONJ).PATIENTS AND METHODS: We reviewed data relating to 398 patients treated with intravenous BP for bone metastases, checking their serum creatinine levels throughout the treatment period in order to assess renal function, and seeking any signs and symptoms of ONJ recorded in their medical records. We also analysed other risk factors for renal toxicity and ONJ in patients who developed them.RESULTS: The median treatment period was 14 months (range 1-119); 108 patients received BP for more than 1 year, and 112 for more than 2 years. Sixteen patients (4%) developed renal toxicity after a median of 24 months of BP treatment, eight of them had been treated for more than 2 years. Ten patients (2.5%) were diagnosed as having ONJ after a median of 39 months on BP, only three of them had been treated for less than 2 years. Two patients experienced both ONJ and renal toxicity.CONCLUSIONS: The low incidence of ONJ and renal toxicity indicates the safety of BP. However, prevention and early detection are still the "first-line therapy" for decreasing their occurrence further

Anti-Inflammatory Activity of Exopolysaccharides from Phormidium sp. ETS05, the Most Abundant Cyanobacterium of the Therapeutic Euganean Thermal Muds, Using the Zebrafish Model

The Euganean Thermal District (Italy) represents the oldest and largest thermal center in Europe, and its therapeutic mud is considered a unique product whose beneficial effects have been documented since Ancient Roman times. Mud properties depend on the heat and electrolytes of the thermal water, as well as on the bioactive molecules produced by its biotic component, mainly represented by cyanobacteria. The investigation of the healing effects of compounds produced by the Euganean cyanobacteria represents an important goal for scientific validation of Euganean mud therapies and for the discovering of new health beneficial biomolecules. In this work, we evaluated the therapeutic potential of exopolysaccharides (EPS) produced by Phormidium sp. ETS05, the most abundant cyanobacterium of the Euganean mud. Specifically, Phormidium EPS resulted in exerting anti-inflammatory and pro-resolution activities in chemical and injury-induced zebrafish inflammation models as demonstrated using specific transgenic zebrafish lines and morphometric and expression analyses. Moreover, in vivo and in vitro tests showed no toxicity at all for the EPS concentrations tested. The results suggest that these EPS, with their combined anti-inflammatory and pro-resolution activities, could be one of the most important therapeutic molecules present in the Euganean mud and confirm the potential of these treatments for chronic inflammatory disease recovery

MOESM8 of Generation of donor-specific Tr1 cells to be used after kidney transplantation and definition of the timing of their in vivo infusion in the presence of immunosuppression

Additional file 8. Tr1 cell sorting gating strategy

Toward a sustainable maze cropping: X-omics support the understanding of the effects of some biotechnological practices

The adoption of more sustainable practices in maize cropping may be hampered by the challenges posed by climate change if the same do not also improve the resilience of the system to more stressing environment. The exploitation of beneficial microorganisms as bioinoculants appears as an environmental-friendly biotechnological tool in maize cropping as they can reduce requirements of inorganic fertilizers by positively influencing soil fertility. Biochar addition to soil is a promising strategy for climate change mitigation and soil fertility improvement. The objectives of this study were to unravel the synergistic effect of co-applied biochar and synthetic microbial consortia (SMC) or arbuscular mycorrhizal fungi on maize growth, soil microbiome and grain metabolome. Field experiments were carried out in two growing seasons in Italy. At different vegetative growth stages, both physiological parameters and soil chemical composition were evaluated. At harvest, yield performance was assessed, and maize kernels were collected to perform global metabolomic profiling. Rhizosphere microbial ecosystem was investigated by 16S metabarcoding sequencing and bioinformatic tools. SMC application did not significantly affect the microbial communities in terms of diversity and richness of species, with a low risk of a long-term impact on the ecology of the indigenous microbial population. However, biochar exerted a great impact on rhizosphere soil microbiome, suggesting that functionalization of biochar with SMC seems a promising approach for microbiome modulation and for enhancing plant growth also in limiting environments. Larger effects were found on the grain at metabolomic level on the presence of different fatty acids, aminoacids, and lipids

PI3KCA mutations and/or PTEN loss in Her2-positive breast carcinomas treated with trastuzumab are not related to resistance to anti-Her2 therapy.

Purpose: to evaluate whether activating mutations of the p110α catalytic subunit of class A phosphoinositide 3-kinases (PI3KCA) or complete loss of PTEN are associated with response to anti-Her2 treatment in breast cancer (BC). Experimental Design: we analyzed PI3KCA hot-spot mutations and PTEN immunohistochemical expression in 129 Her2-positive IBC treated with trastuzumab, including 26 cases treated with neoadjuvant therapy, 48 metastatic IBC (MBC) and 55 early stage IBC, with complete clinical information (mean follow-up 37, 66 and 32 months, respectively). Results: PI3KCA hot-spot mutations were observed in 25 cases (19.4%): 12 (9.3%) in exon 9 and 13 (10.1 %) in exon 20. No relationships were observed between mutations and pathological and biological parameters. In patients treated with neoadjuvant therapy and in MBC we could not observe any relationship with response to trastuzumab-based therapy. PTEN loss was observed in 24 out of 86 informative cases (28%), 3 (12.5%) of which were also mutated for PI3KCA. PI3K pathway activation, defined as PI3KCA mutation and/or PTEN loss, was not associated with response to treatment or clinical outcome in MBC. Conclusion: PI3KCA mutation and/or PTEN loss should not exclude patients from potentially beneficial anti-Her2 therapy